ABSTRACT Genomic DNA constantly suffers various insults from endogenous and endogenous sources of DNA damage. Fortunately, cells possess various genome maintenance pathways to repair these DNA lesions. It is now known that defects in any of these pathways lead to genome instability and a variety of human diseases, including cancer. Equally, DNA repair activity can also render cancer cells more tolerant to many therapeutic drugs. Recent studies have demonstrated that patients with tumors defective in DNA mismatch repair (MMR) respond very positively to immunotherapy via PD-1/PDL-1 blockade. However, the molecular mechanisms underlying these processes are not well understood. The purpose of this R13 application is to provide partial financial support for a Special Symposium entitled Genome Maintenance Systems in Cancer Etiology and Therapy: A Tribute to Dr. Paul Modrich to address the current challenges. Dr. Modrich, a 2015 Nobel Laureate in Chemistry, is responsible for elucidating the mechanisms of MMR in both bacteria and humans, and he has demonstrated that MMR inactivation leads to the most common form of hereditary colon cancer and results in tumor resistance to therapeutic drugs. The focus of the symposium is to bring together scientists working at the cutting edge of current efforts to elucidate the molecular mechanisms of DNA repair and their roles in cancer etiology and therapy that were pioneered by Dr. Modrich in order to stimulate discussions and to further cross-fertilize ideas at the forefront of the field. The program will bring together a diverse group of world leaders and expertise in DNA repair to jointly consider how recent advances inform our understanding of the impact(s) of DNA repair defects/variants in cancer development and treatment. Based on their expertise in this field, we will include women, minorities, and persons with disabilities in the planning and implementation of, and participation in, the proposed symposium. In addition to invited talks, the program will also include ?poster flash? platform presentation sessions as part of the schedule, ensuring that contributions and participation by students, postdoctoral fellows, and early career scientists receive ample attention, and their attendance at the symposium will be actively sought and strongly encouraged. The objective of this application is to seek partial financial support for the Symposium, primarily for travel related expenses of 15-invited speakers who are not in the Washington D.C. metropolitan area. Since registration fees will cover less than half of the cost of the Symposium, external support is essential to holding this cutting-edging and timely Special Symposium in the honor of Dr. Paul Modrich and his pioneering discoveries in the field of DNA repair, cancer etiology, and novel therapeutic approaches to prevent and/or treat cancer, as well as to inspiring the next-generations of scientists to follow in the footsteps of these world leaders in facing the scientific challenges of the 21st century.